Cancers, Vol. 13, Pages 1901: Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC

Cancers, Vol. 13, Pages 1901: Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC Cancers doi: 10.3390/cancers13081901 Authors: Eleni Skavatsou Maria Semitekolou Ioannis Morianos Theodoros Karampelas Nikolaos Lougiakis Georgina Xanthou Constantin Tamvakopoulos Pioneering studies on tumor and immune cell interactions have highlighted immune checkpoint inhibitors (ICIs) as revolutionizing interventions for the management of NSCLC, typically combined with traditional MTD chemotherapies, which usually lead to toxicities and resistance to treatment. Alternatively, MTR chemotherapy is based on the daily low dose administration of chemotherapeutics, preventing tumor growth indirectly by targeting the tumor microenvironment. The effects of MTR administration of an oral prodrug of gemcitabine (OralGem), alone or with anti-PD1, were evaluated. Relevant in vitro and in vivo models were developed to investigate the efficacy of MTR alone or with immunotherapy and the potential toxicities associated with each dosing scheme. MTR OralGem restricted tumor angiogenesis by regulating thrombospondin-1 (TSP-1) and vascular endothelial growth factor A (VEGFA) expression. MTR OralGem enhanced antitumor immunity by increasing T effector responses and cytokine release, concomitant with dampening regulatory T cell populations. Promising pharmacokinetic properties afforded minimized blood and thymus toxicity and favorable bioavailability u...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research